14-68259109-T-A

Variant names:

• chr14-68259109-T-A
• rs17105269
• NM_133510.4:c.757-32775T>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_133510.4(RAD51B):​c.757-32775T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.302 in 152,140 control chromosomes in the GnomAD database, including 11,236 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.30 (11236 hom., cov: 31)
• Consequence: RAD51B NM_133510.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.124
• Publications: 4 publications found

Genes affected

RAD51B (HGNC:9822): (RAD51 paralog B) The protein encoded by this gene is a member of the RAD51 protein family. RAD51 family members are evolutionarily conserved proteins essential for DNA repair by homologous recombination. This protein has been shown to form a stable heterodimer with the family member RAD51C, which further interacts with the other family members, such as RAD51, XRCC2, and XRCC3. Overexpression of this gene was found to cause cell cycle G1 delay and cell apoptosis, which suggested a role of this protein in sensing DNA damage. Rearrangements between this locus and high mobility group AT-hook 2 (HMGA2, GeneID 8091) have been observed in uterine leiomyomata. [provided by RefSeq, Mar 2016]

RAD51B Gene-Disease associations (from GenCC):

• primary ovarian failure

  Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.672 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RAD51B	NM_133510.4	c.757-32775T>A		intron_variant	Intron 7 of 10	ENST00000471583.6	NP_598194.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RAD51B	ENST00000471583.6	c.757-32775T>A		intron_variant	Intron 7 of 10	1	NM_133510.4	ENSP00000418859.1

Frequencies

GnomAD3 genomes AF: 0.302 AC: 45851 AN: 152022 Hom.: 11183 Cov.: 31

Gnomad AFR AF: 0.678

Gnomad AMI AF: 0.135

Gnomad AMR AF: 0.224

Gnomad ASJ AF: 0.279

Gnomad EAS AF: 0.0202

Gnomad SAS AF: 0.165

Gnomad FIN AF: 0.116

Gnomad MID AF: 0.415

Gnomad NFE AF: 0.153

Gnomad OTH AF: 0.306

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.302 AC: 45955 AN: 152140 Hom.: 11236 Cov.: 31 AF XY: 0.295 AC XY: 21966 AN XY: 74390

African (AFR) AF: 0.678 AC: 28120 AN: 41456

American (AMR) AF: 0.223 AC: 3413 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.279 AC: 969 AN: 3470

East Asian (EAS) AF: 0.0200 AC: 104 AN: 5188

South Asian (SAS) AF: 0.164 AC: 794 AN: 4832

European-Finnish (FIN) AF: 0.116 AC: 1230 AN: 10594

Middle Eastern (MID) AF: 0.429 AC: 126 AN: 294

European-Non Finnish (NFE) AF: 0.153 AC: 10437 AN: 67994

Other (OTH) AF: 0.302 AC: 639 AN: 2114

Alfa AF: 0.234 Hom.: 902

Bravo AF: 0.328

Asia WGS AF: 0.150 AC: 523 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	6.9
DANN	Benign	0.86
PhyloP100		0.12
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs17105269; hg19: chr14-68725826;